Control of Amphiphile Self-Assembling at the Molecular Level: Supra-Molecular Assemblies with Tuned Physicochemical Properties for Delivery Applications 1271 ACS SYMPOSIUM SERIES Control of Amphiphile Self-Assembling at the Molecular Level: Supra-Molecular Assemblies with Tuned Physicochemical Properties for Delivery Applications Marc A. Ilies, Editor Temple University School of Pharmacy Philadelphia, Pennsylvania Sponsored by the ACSDivisionofColloidandSurfaceChemistry AmericanChemicalSociety,Washington,DC DistributedinprintbyOxfordUniversityPress LibraryofCongressCataloging-in-PublicationData Names:Ilies,MarcA.,editor.|AmericanChemicalSociety.Divisionof ColloidandSurfaceChemistry. Title:Controlofamphiphileself-assemblingatthemolecularlevel: supra-molecularassemblieswithtunedphysicochemicalpropertiesfor deliveryapplications/MarcA.Ilies,editor,TempleUniversitySchoolof Pharmacy,Philadelphia,Pennsylvania;sponsoredbytheACSDivisionof ColloidandSurfaceChemistry. Description:Washington,DC:AmericanChemicalSociety,[2017]|Series:ACS symposiumseries;1271|Includesbibliographicalreferencesandindex. Identifiers:LCCN2017052433(print)|LCCN2017054832(ebook)|ISBN 9780841232730(ebook)|ISBN9780841232747 Subjects:LCSH:Amphiphiles.|Self-assembly(Chemistry)|Biological transport.|Supramolecularchemistry. Classification:LCCQD382.A47(ebook)|LCCQD382.A47C662017(print)|DDC 615.1/9--dc23 LCrecordavailableathttps://lccn.loc.gov/2017052433 ThepaperusedinthispublicationmeetstheminimumrequirementsofAmericanNational Standard for Information Sciences—Permanence of Paper for Printed Library Materials, ANSIZ39.48n1984. Copyright©2017AmericanChemicalSociety DistributedinprintbyOxfordUniversityPress AllRightsReserved. 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Registerednames,trademarks,etc.,usedinthispublication,evenwithout specificindicationthereof,arenottobeconsideredunprotectedbylaw. PRINTEDINTHEUNITEDSTATESOFAMERICA Foreword The ACS Symposium Series was first published in 1974 to provide a mechanism for publishing symposia quickly in book form. The purpose of the series is to publish timely, comprehensive books developed from the ACS sponsoredsymposiabasedoncurrentscientificresearch. Occasionally,booksare developed from symposia sponsored by other organizations when the topic is of keeninteresttothechemistryaudience. Beforeagreeingtopublishabook,theproposedtableofcontentsisreviewed forappropriateandcomprehensivecoverageandforinteresttotheaudience. Some papersmaybeexcludedtobetterfocusthebook;othersmaybeaddedtoprovide comprehensiveness. When appropriate, overview or introductory chapters are added. Draftsofchaptersarepeer-reviewedpriortofinalacceptanceorrejection, andmanuscriptsarepreparedincamera-readyformat. As a rule, only original research papers and original review papers are included in the volumes. Verbatim reproductions of previous published papers arenotaccepted. ACSBooksDepartment Contents Preface.............................................................................................................................. ix 1. SyntheticDeliverySystemsforDNA,siRNA,andmRNABasedon PyridiniumAmphiphiles ......................................................................................... 1 MarcAIlies,UttamSatyal,andVishnuD.Sharma 2. DesigningPolymerMicellesofControlledSize,Stability,andFunctionality forsiRNADelivery................................................................................................. 35 ChristinaM.Bailey,RamanathanNagarajan,andTerriA.Camesano 3. UtilizingCholesterolNanodomainsforNucleicAcidDelivery.......................... 71 JamieL.Betker,LongXu,YeZhang,andThomasJ.Anchordoquy 4. InSilicoSelf-AssemblyofNanoparticleswithApplicationsinDrug Delivery ................................................................................................................... 95 EditheSelwaandBogdanI.Iorga 5. CharacterizingPEGChainsTetheredontoMicellesandLiposomesApplied asDrugDeliveryVehiclesUsingScatteringTechniques .................................. 115 ShotaFujii,MinaSakuragi,andKazuoSakurai 6. StrategiesforFunctionalizingLipoprotein-BasedNanoparticles ................... 131 SeanF.Gilmore,WeiHe,AmyRasley,andNicholasO.Fischer 7. RationallyControlledSelf-AssemblyBehaviorofInorganic-Organic HybridsinSolution .............................................................................................. 151 YangChuandTianboLiu 8. Sn2LipaseLabileProdrugsandContact-FacilitatedDrugDeliveryfor Lipid-EncapsulatedNanomedicines................................................................... 189 D.Pan,G.Cui,C.T.N.Pham,M.H.Tomasson,K.N.Weilbaecher,andG.M.Lanza 9. Interface-EngineeredAmphiphilicBlockCopolymerswithTuned EnzymaticResistanceforControlledDeliveryofChemotherapeutic Drugs ..................................................................................................................... 211 UttamSatyal,VishnuDuttSharma,JenniferA.Shif,andMarcA.Ilies 10. BiocompatibleNanoparticlesforSelectiveDrugReleaseatCancerCells ..... 231 FilizKaragöz,RobertDorresteijn,KlausMüllen,andMarkusKlapper vii 11. InverseFlashNanoPrecipitationforBiologicsEncapsulation: Nanoparticle FormationandIonicStabilizationinOrganicSolvents ................................... 249 RobertF.PagelsandRobertK.Prud’homme 12. Inverse Flash NanoPrecipitation for Biologics Encapsulation: UnderstandingProcessLossesviaanExtractionProtocol .............................. 275 ChesterE.MarkwalterandRobertK.Prud’homme 13. EngineeredCellPenetratingPeptides................................................................ 297 WeiliMaandWonH.Suh Editor’sBiography....................................................................................................... 321 Indexes AuthorIndex ................................................................................................................ 325 SubjectIndex................................................................................................................ 327 viii Preface This book has its sources in the symposium with the same title, held at the 252nd ACS National Meeting in Philadelphia, PA on August 21–25, 2016. The symposiumwassponsoredbytheACSDivisionofColloidandSurfaceChemistry, aspartofitscontinuingsymposiaonamphiphilesandtheirself-assemblies. Iam indebted to Dr. Ramanathan Nagarajan (Natick Soldier Research, Development &EngineeringCenter,Natick,MA),ProgramChairforACSDivisionofColloid and Surface Chemistry, for his efforts to accommodate this symposium, for his scientific contributions to the symposium and to this book, and for his constant support. The main focus of the book is the design, synthesis and characterization of amphiphile self-assemblies and the dynamic assessment of these assemblies as delivery systems for drugs and nucleic acids. As delivery systems, these supra-molecular assemblies have the ability to change the pharmacokinetics and volume of distribution of their cargo, to protect it from premature decomposition or inactivation, and to control the spatial-temporal location and duration of the therapeutic effect associated with cargo delivery. Many biocompatible/biodegradable delivery systems present in the market today or in advanced clinical trials are made of self-assembled amphiphilic molecules of different types and molecular weights. Their physicochemical and delivery abilitiesaredeterminedbyphysicochemicalparametersofindividualamphiphiles and of the loaded cargo. Therefore, substantial efforts were made towards the design of novel amphiphiles with encapsulation and delivery properties tailored fordifferentcargosandfordifferentbiologicalapplications. Different chapters of the book present delivery systems made out of large variety of amphiphiles, including simple surfactants, gemini surfactants, pseudo-gemini surfactants, lipids, lipophilic polycations, dendrimers, natural and synthetic polymers and their conjugates. The cargo encapsulated by these amphiphiles is quite diverse too: chemotherapeutic cytotoxic drugs, peptide, proteins, nucleic acids (pDNA, siRNA, mRNA). The book also presents the formulation protocols and parameters used in the component or cargo loading process, with theoretical support and rationale. It reveals how formulation technology can affect the drug loading ability, physicochemical properties, dynamicstabilityandunloadingpropertiesofthedeliverysystem,acrossdifferent classesofamphiphilesandcargos. Twomaindifferentstrategiesarecurrentlyusedinthedesignofamphiphile- based delivery systems for drugs and nucleic acids. In formulation-based strategies, amphiphiles of different packing parameters and physicochemical properties are blended together, simultaneously or sequentially with the cargo, ix